Satoh S, Tanaka A, Hatano E, Inomoto T, Iwata S, Kitai T, Shinohara H, Tsunekawa S, Chance B, Yamaoka Y
Second Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Gastroenterology. 1996 Apr;110(4):1166-74. doi: 10.1053/gast.1996.v110.pm8613006.
BACKGROUND & AIMS: The catalysis of a creatinine/phosphocreatine system by creatine kinase is not expressed in the liver. The aim of this study was to examine the energy energy metabolism and regeneration after hepatectomy using transgenic mouse liver expressing creatine kinase to clarify the effects of phosphocreatine on liver regeneration.
Transgenic mice were divided into two groups: group 1 was fed normal chow, and group 2 was fed 10% creatine chow for 5 days. Hepatic energy metabolism was evaluated before and after hepatectomies. Changes in remnant liver weight gain and bromodeoxyuridine labeling index were measured after 70% and 80% hepatectomies.
Hepatic adenosine triphosphate level 24 hours after 70% hepatectomy was significantly higher in group 2 than group 1 (P<0.05). In group 2, mitochondrial adenosine triphosphate synthesis was enhanced because of elevated intramitochondrial adenine nucleotide content before hepatectomy, leading to sufficient adenosine triphosphate synthesis after a 70% hepatectomy. Bromodeoxyuridine DNA labeling index 24 hours after a 70% hepatectomy was significantly higher in group 2 than group 1. Rapid liver weight gain was observed in group 2 after a 70% hepatectomy.
Abundant phosphocreatine promotes liver regeneration by reinforced hepatic energy metabolism. Gene transfer of creatine kinase to the liver may be a potential method in liver surgery.
肌酸激酶对肌酐/磷酸肌酸系统的催化作用在肝脏中未表达。本研究的目的是利用表达肌酸激酶的转基因小鼠肝脏,检测肝切除术后的能量代谢和再生情况,以阐明磷酸肌酸对肝脏再生的影响。
将转基因小鼠分为两组:第1组喂正常饲料,第2组喂含10%肌酸的饲料,持续5天。在肝切除术前和术后评估肝脏能量代谢。在70%和80%肝切除术后,测量残余肝脏重量增加和溴脱氧尿苷标记指数的变化。
70%肝切除术后24小时,第2组肝脏三磷酸腺苷水平显著高于第1组(P<0.05)。在第2组中,由于肝切除术前线粒体内腺嘌呤核苷酸含量升高,线粒体三磷酸腺苷合成增强,导致70%肝切除术后有足够的三磷酸腺苷合成。70%肝切除术后24小时,第2组溴脱氧尿苷DNA标记指数显著高于第1组。70%肝切除术后,第2组观察到肝脏重量快速增加。
丰富的磷酸肌酸通过增强肝脏能量代谢促进肝脏再生。将肌酸激酶基因转移至肝脏可能是肝脏手术中的一种潜在方法。